DD283320A5 - FUNGICIDE PYRIDYLCYCLOPROPANCARBOXAMIDINE - Google Patents

Abstract

The invention relates to fungicidal compositions. According to the invention, the novel compositions contain as active ingredient new fungicidal pyridylcyclopropanecarbamidine derivatives having the general structural formula and tautomers thereof, wherein R is hydrogen, a pyridyl, a substituted pyridyl, a C1-C3 alkoxy, a C1-C6 alkyl, a Acyl, carbamoyl, sulfonyl or cyano group; R 1 is halogen, a C 1 -C 3 alkenyloxy group or a C 1 -C 3 alkoxy group; R2 is hydrogen or a C1-C3 alkyl group; R3 is hydrogen, an alkyl, aryl or arylalkyl group, and suitable as fungicides, organic and inorganic salts thereof, in addition to carrier agents and / or surface-active agents. Formula {fungicidal activity; healing effect; Application; Fighting fungi in horticulture and agriculture}

Description

OCH

; R ^{1 is} an -OCH, group

and R ^{2 is} Cl.

3. Compositions according to claim 1, characterized in that R is a -CH ₃ group, R ^{1 is} an -OCH ₃ -GrUpPe, R ² -H and R ^{3 is} an-OCH ₃ group.

4. A method of controlling fungi, characterized in that in the area where a control is desired, a fungicidally effective amount of a compound of formula

and tautomers thereof, wherein R is hydrogen, a pyridyl, a substituted pyridyl, a C ₁ -C ₃ alkoxy, a C ₁ -C 6 alkyl, an acyl, carbamoyl, sulfonyl or cyano group; R ^{1 is} hydrogen, a C ₁ -C ₃ -alkoxy or Ci-CrAlkenyloxygruppe; R ^{2 is} hydrogen or a C 1 -C 5 alkyl group; R ^{3 represents} hydrogen, an alkyl, aryl or arylalkyl group, as well as fungicide suitable organic and inorganic salts thereof is used. 5. The method according to claim 4, characterized in that R is a

/ Λ-

1 2

OCH moiety, R -OCH ₃ and R Cl

mean.

6. The method according to claim 4, characterized in that R represents a CH ₃ group, R ^{1 3} is a -0CH represent an -OCH ₃ group, R ² is -H and R ₃ group.

Field of application of the invention

The invention relates to fungicidal compositions for use in horticulture and agriculture.

Characteristic of the known state of the art

The infection of crops such as barley, rice, tomatoes, wheat, beans, roses, citrus fruits and other agriculturally important species by fungi can lead to severe losses in both the quantity and the quality of agricultural products. It is therefore highly desirable to have available means by which the

Growth of fungi is prevented, combated or excluded. In many cases, preventive spraying with commercially available fungicides attempts to prevent the appearance and growth of fungi on agriculturally important products.

ZIoI the invention

The object of the invention is to provide fungicides having a curative effect which, upon detection of infection by fungi, can combat these fungi and which can eliminate the adverse effects which may be incurred by the use of sprays after infection.

Explanation of the essence of the invention

The invention is based on the Aufgi ib found new compounds that are suitable as an active ingredient in fungicidal compositions with the desired properties.

According to the invention novel fungicidal Pyridylcyclopropancarbamidine with the general formula

and tautomers thereof, wherein R is hydrogen, a pyridyl, a substituted pyridyl, a C, -C ₃ alkoxy, a C) -C _e alkyl, acyl, carbamoyl, sulfonyl or cyano group ; R ^{1 is} halogen, such as chlorine, fluorine and bromine, a C ₁ -C ₃ -alkoxy group, such as a propoxy group, ethoxy group or methoxy group, preferably a methoxy group, and a C 1 -C ₃ -alkenyloxy group; R ^{2 is} hydrogen or a C 1 -C ₃ alkyl group, preferably a methyl group, and R ^{3 is} hydrogen, an alkyl, aryl or arylalkyl group, as well as fungicides effective organic and inorganic salts thereof, the highly effective fungicides for use both as a preventive as well as healing fungicides. When R ^{3 is} hydrogen, the compounds of the invention may occur in tautomeric forms

and the above formula with R ³ should be considered to include these tautomers.

The term "fungicide" is used to refer to a compound that controls the growth of fungicides, and the term "controlled" includes the prevention, destruction and inhibition of growth of fungi. The term "curative" is used to refer to the application of the fungicide after infection, thereby providing control of the infection by fungi and preventing the development of adverse effects of the fungi on the host plants.

Novel, fungicidal compounds according to the invention are Pyridylcyclopropancarbamidine the general formula

and tautomers thereof, wherein R is hydrogen, a pyridyl, substituted pyridyl, C ₁ -C ₃ -alkoxy, C ₁ -C 6 -alkyl, acyl, carbamoyl, sulfonyl or cyano group; R ¹ halogen such as chlorine, fluorine or bromine, a C | -C ₃ alkoxy such as propoxy, ethoxy or methoxy, preferably methoxy group, and an alkenyloxy group dC _3; R ^{2 is} hydrogen and a C) -C ₃ alkyl group, preferably a methyl group; R ^{3 is} hydrogen, an alkyl, aryl or arylalkyl group, and suitable as fungicides are organic and inorganic salts thereof, which are highly effective fungicides for use both as preventive and as curative fungicides, are described herein. When R ^{3 is} hydrogen, the compounds of the invention may be in the tautomeric form

and the above formula with R ³ should be considered as including these tautomers.

The compounds of the invention can generally be prepared by a multistage process. The first step is the reaction of a suitably substituted aminopyridine with a suitably substituted cyclopropanecarboxylic acid chloride in an inert solvent such as methylene chloride, chloroform, hexane or toluene in a suitable reaction vessel. Optionally, during the reaction, an acid scavenger such as pyridine, a trialkylamine, an alkali carbonate or an alkylhydroxide may be present.

Depending on the reaction conditions, the reaction is carried out at room temperature, but may be carried out in a temperature range of -30 to 80 ° C. Depending on the reaction temperature, the reaction will be completed in up to three hours. The solid intermediate thus prepared can be isolated by conventional methods, e.g. Example by washing with an alkaline solution, separation of the solid product by filtration, when this intermediate is formed in the reaction as a solid, or by drying and evaporation of the reaction solution, whereby the desired first intermediate product is obtained. The second step is the reaction of the dry product from the first reaction with an imidoylating agent such as phosphorus pentachloride in an inert solvent such as methylene chloride or the like. This reaction may be carried out at room temperature or at the reflux temperature of the methylene chloride. Evaporation of the solvent in vacuo gives the hydrochloride of imidoyl chloride as a second intermediate.

This obtained as an intermediate imidoyl chloride is reacted with an excess of ammonia, suitably substituted amine or hydroxylamine in the cold at -30 to -80 ° C in an inert solvent such as ether or methylene chloride. After the reaction is complete, the reaction mixture is warmed to room temperature and washed with water. Separation, drying and evaporation of the solvent lead to the product, the amidine. This amidine-type product may be further reacted in an inert solvent such as ether or methylene chloride with a suitably substituted isocyanate. After completion of the reaction, the reaction product can be isolated by distilling off the solvent, whereby the desired carbamoylamidine is obtained. The amidine-type product may also be further reacted with suitable acid chlorides, sulfonyl chlorides, carbamoyl chlorides or phosphoryl chlorides in an inert solvent such as methylene chloride in the presence of an acid scavenger such as pyridine. After appropriate washing with water and / or bicarbonate solution, drying and distilling off the solvent, the desired acyl, sulfonyl, carbamoyl or Phosphorylamidin derivative can be obtained.

embodiment

The invention is explained in more detail below with reference to some examples.

example 1

Preparation of N- (2-methoxypyrid-5-yl) cyclopropane carbamate

12.4 g of 5-amino-2-methoxy-pyridine (0.10 mol) and 10 ml of pyridine were mixed together in 200 ml of methylene chloride in a reaction flask. To reader's reaction mixture, 9.1 mL of cyclopropanecarboxylic acid chloride (0.10 mol) was added over 2 minutes. The reaction was exothermic and the temperature rose to 34 ° C. The reaction mixture was allowed to stand for one hour at room temperature and then washed with 200 ml of 5% sodium hydroxide solution and 100 ml of water. The organic phase thus obtained was separated and dried over anhydrous magnesium sulfate. Crystals formed, so that the mixture was filtered and washed with 300 ml of acetone. The filtrate was evaporated in vacuo to give a solid which was slurried with hexane. This gave 16.7 g after drying. The product was (NMR) identified by infrared (IR) and nuclear magnetic resonance spectroscopy as the title compound, melting point 130-131 ⁰ C.

Example 2

Preparation of 2- (methoxypyrid-5-yl) cyclopropane carbimidoyl chloride

In a reaction flask, 50 ml of methylene chloride and 10.4 g of phosphorus V chloride (0.05 mol) were mixed together. Under nitrogen, 9.0 g of N- (2-methoxypyrid-5-yl) cyclopropanecarbamide (0.05 mol) was added thereto in several portions with stirring. The reaction was exothermic. The reaction mixture was stirred for one hour at room temperature and then refluxed for an additional hour with stirring to dissolve and react the solids in the reaction vessel. The reaction mixture was then evaporated in vacuo to give a solid product, which was washed twice with 50 mL each of ether and dried in vacuo to give 12.0 g of a solid which was identified by nuclear magnetic resonance spectra as the title compound.

Example 3

Preparation of N- (2-methoxypyrid-5-yl) cyclopropanecarbamide

In a mixture of 7.5 g of N- (2-methoxypyrid-5-yl) cyclopropancarbimidoylchlorid and 200 mL of methylene chloride was bJ -40 ⁰ C initiated an excess of ammonia over 40 minutes. The reaction mixture was allowed to warm to 10 ⁰ C and washed with 50 mL of water, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a solid which was washed with ether to give 2.5 g of the desired product F = 121- 124 ^° C. The product was identified by IR, NMR and mass spectroscopy. Representative compounds of the invention and their properties are shown in Table I. Table I

Table I

No _{0 of} the connection

³ n ³⁰ or F ( ⁰ O)

-0OH .

-0OH

-H

-ONHOH

-00H,

-ooh '-ooh' -ooh '

-OCH

Oil -H when 85 ⁰ O hydrochloride H -H 3 oil H --OOH oil H -H . 121.0 to 124, ⁰ O O H -H 144.0-146.0 ⁰ O H - ^ H $ 8, 0 to 94.0 ° 0

-H

-H -H

115,0-119, Ο ^υ Ο

81.0-88.0 ⁰ O

92.0-95, O ⁰ C

Example 4 Method of Evaluating Preventive Spraying Powdery Mildew on Barley (BPM)

Northrup King Sunbar 401 barley seed is seeded with 12 seeds per 2 "pot in sandy loam soil seven days prior to testing The compound to be tested is dissolved with a 50:50 mixture of acetone: water so that concentrations of 750pg 12 ml of the test solution are sprayed onto the barley plants with a sprayer and after 24 hours the test substances are placed in an infection box with a circulating fan.

Directly in front of the fan are barley plants with strongly spore-containing places with Erysiphe graminis placed in order to separate the spores from the plants and to distribute. After two minutes, the fan is turned off and the box held closed for five minutes to allow the spores to settle. The infected plants are then placed on greenhouse benches

with automatic irrigation from below.

The results are recorded seven days after infection as percent of disease control based on percent reduction in infected area compared to untreated control plants. The concentrations of the compounds leading to a 90% disease control (EC 90) are calculated from dosing

Dilution curves determined. Rice brandy (RB)

Ten seeds of the Calrose M-9 rice variety are sown in sandy loam soil in two-inch pots 12 days before the test.

the compound to be tested is dissolved with a 50:50 mixture of acetone and water, whereby concentration descending from 750pg / ml is obtained. Twelve ml of the test solution are sprayed onto the rice plants with atomizers.

The inoculum is prepared from three week old cultures of Pyricularia oryzae grown on rice polish agar.

The agar is first flooded with deionized water, the spores separated from the surface by gentle rubbing, and then diluted to 5 x 10 ⁶ spores / ml with deionized water plus 0.05% Tween ™ 24 hours after application of the compound Infected plants by spraying the spore suspension to drainage, allowing it to dry on the leaves, splashing again until it drains, and then placing the plants in a moist chamber. After 48 hours in the moist room, the plants were planted on greenhouse. Benches with

automatic irrigation spent from below.

The results were recorded seven days after infection as percent of disease control based on the reduction of infestation in infested areas compared to untreated control plants. The

(750) ft 200 » » 750 750 » 70 • » 700 ft ft 600 750 ί SO) 750 (750) It ft * , 750) » ft 750

Concentration of the compounds leading to a 90% disease control (EC 90) is determined from dose dilution curves

 Gray horse (BB)

Two petals of a white rose are placed in a Petri dish lined with damp filter paper. The compound to be tested is dissolved in a 50:50 mixture of acetone and water and diluted to 750pg concentrations in descending order. Half a ml of the test solution is sprayed onto the petals and then allowed to dry. The inoculum is prepared by adding a 5 mm spot of a two week old culture of Botrytis cinerea grown on Elliot V-8 agar along with 0.5 ml of grapefruit juice to 10 ml of sterile, distilled water. A drop of 20 μΙ of this inoculum is placed on each petal. The Petri dishes with the infected petals are stored in sealed plastic containers to constantly have a saturated with moisture atmosphere. Results are recorded four days after infection as percent reduction in necrosis area compared to controls with acetone: water. The concentration of the compound resulting in a 90% disease control (EC 90) is determined from dose dilution curves. The results are given in Table II as approximate EC 90 values in parts per million (ppm) '750μg / ml equivalent to 750ppm). The entry (750) indicates partial control at 750ppm. A star (') indicates no control at a concentration of 750ppm.

Table II

No. of connection PM RB BB

The compounds of the present invention are particularly effective against gray mold and, in particular, are effective as preventive foliar spray and healing foliar spray when compared to the commercial standard agents used as preventive and curative sprays in gray horse. The compounds according to the invention are particularly active against fungi such as Erysiphe graminis and Pyricularia oryzae. The compounds of the invention are useful as fungicides, particularly as preventive or curative fungicides, and can be used in a variety of ways at a variety of concentrations. In general, these compounds and compositions with these compounds can be applied directly to the foliage of the crops, the soil in which the crops grow, or the irrigation water for the crops or the soil. In practice, the compounds herein defined are compounded into fungicidal compositions by blending in amounts effective as fungicides with the adjuvants and vehicles commonly used to improve the distribution of active ingredients for agricultural use, taking into account the fact that the composition and mode of application of a toxic compound may affect the activity of the substance in a given application. Thus, these fungicidally active compounds may be formulated in the form of wettable powders, as emulsifiable concentrates, as powdered dusts, as solutions, or as another of the many known forms of the compositions, depending on the desired mode of application. Preferred compositions for use as preventive or curative fungicides are wettable powders and emulsifiable concentrates. These compositions may contain only 0.1% and up to 95% or more by weight of the active ingredient. The effective amount of fungicides depends on the nature of the seed or plants to be treated, and the amount of application is between 0.05 and about 25 pounds per pound, preferably about 0.1 to about 10 pounds per pound ,

Wettable powders are in the form of finely divided particles that can be readily dispersed in water or other dispersants. The wettable powder is finally applied to the soil or plants either as a dry dust or as a dispersion in water or other liquid. Typical carriers for wettable powders are Fuller's earth, Koalintone, silicic acid or other readily wettable organic or inorganic diluents. Wettable powders are usually prepared to contain about 5% to about 95% active ingredient and also contain a small amount of virgin agent, dispersing aid or emulsifier to facilitate wetting and dispersion. Dry flowable or water dispersible granules are agglomerated wettable powders prepared either by disk granulation or in fluidized beds. The dry flowable material is ultimately applied to the soil or plants as a dispersion in water or other liquid. These granules are dust-free and free-flowing when dry, and still form homogeneous dispersions when diluted with water. Typical carriers for dry flowable compositions are i.a. Fuller's earth, koalintone, silica and other readily wettable organic and inorganic diluents. The dry flowable compositions are generally prepared to maintain between about 5% and about 95% of the active ingredient and also a small amount of a wetting agent, dispersing aid or emulsifier to facilitate wetting and dispersion.

Emulsifiable concentrates are homogeneous liquid compositions that can be dispersed in water or other dispersant. They may consist entirely of the active compound and a liquid or solid emulsifier or may also contain a liquid carrier such as xylene, heavy aromatic oil, isophorone and other non-volatile organic solvents. For use as a fungicide, these concentrates are in water or another

flue ^; Carrier dispersed and commonly applied as a spray on the surface to be treated. The proportion by weight of the essential active ingredient may vary widely with respect to the use of the composition, but in general the fungicidal composition will contain from about 0.1% to 95% of the active ingredient.

Typical wetting agents, dispersing aids or emulsifiers used in agricultural compositions are e.g. the alkyl and alkylaryl sulfonates and sulfates and their sodium salts, polyhydroxy compounds, and other types of surfactants, a variety of which are commercially available. The surfactant, when used, is usually 0.1 to 15% by weight of the fungicidal composition.

Dusts which are free flowing admixtures of the active ingredient to finely divided solids such as talc, clays, flour and other organic and inorganic solids which serve as dispersing aids and vehicle for the toxic compound are suitable compositions for many applications.

Pastes, the homogeneous suspensions of a finely divided solid toxic substance in a liquid vehicle such as water

or oil are used in special cases. These compositions usually contain from about 5 to about 95 percent by weight of the active ingredient, but may also contain small amounts of wetting agents, dispersing aids or emulsifiers to facilitate distribution. For use, the pastes are usually diluted and applied as a spray on the area to be treated.

Examples of typical compositions

oil

Ingredient% by weight

Compound 1 1

aromatic heavy oil as oily solvent 99

Total 100 emulsifying concentrate

Compound 2 50

Kerosene 45 emulsifier {mixture of long-chain ethoxylated polyethers and

long-chain sulfonates) 5

Total 100 emulsifiable concentrate

Compound 3 90

Kerosene 5 emulsifier (mixture of long - chain ethoxylated polyethers and

long-chain sulfonates) 5

Total 100 dusts and / or powder

Ingredient Weight% Weight% Weight%

Compound 4 0.5 50.0 90.0

Attapulgite flour 93.5 44.0 4.0

Lignosulfonate, sodium salt 5.0 5.0 5.0 sodium salt of sulfosuccinic acid

dioctyl ester 1.0 1.0 1.0

Total 100.0 100.0 100.0

Other suitable compositions for use as a fungicide are further simple solutions of the active ingredient in a dispersing agent in which it is completely soluble in the desired concentration, e.g. Acetone, alkylnaphthalenes, xylene or other organic solvents. Pressurized sprays, usually aerosols, in which the active ingredient is in finely divided form as a result of the evaporation of a low boiling solvent as a carrier, e.g. B. a Freons, can also be used. The fungicidal compositions of the invention are applied to the plants in the usual manner. Thus, the dusty and liquid compositions can be applied to the plants through the use of dryers, machine and hand sprayers and powder sprayers. The compositions may also be applied by aircraft as dust or spray since they are effective even at low dosages.

Claims (1)

Fungicidal compositions, characterized in that they contain a fungicidally effective amount of a compound having the structural formula and tautomers thereof, wherein R is hydrogen, pyridyl, substituted pyridyl, C ₁ -C ₃ alkoxy, C ₁ -C ₆ alkyl, acyl, carbamoyl, sulfonyl or cyano; R ^{1 is} halogen, a C ₁ -C ₃ -alkoxy or Cr-Cr alkenyloxy group; R ^{2 is} hydrogen or a C ₁ -C ₃ alkyl group; R ^{3 is} hydrogen, an alkyl, aryl or arylalkyl group, as well as fungicides suitable organic and inorganic salts thereof, in addition to carriers and / or surface-active agents.
2. Compositions according to claim 1, characterized in that R is a grouping